title: In vivo evaluation of a biodegradable donut-shaped minitablet for prolonged posterior segment drug delivery in the rabbit eye model.
abstract: This study focused on the in vivo evaluation of a biodegradable ganciclovir-loaded donut-shaped minitablet (DSMT) for controlled drug delivery in the New Zealand white albino rabbit eye model. Specialized tablet tooling was used to manufacture a poly(lactic-co-glycolic acid) DSMT device that was implanted into 18 rabbits through the pars plana/peripheral retina of the right eyes of each rabbit. The left eyes were used as controls. Possible adverse effects on ocular tissues were assessed by histomorphology, slit-lamp biomicroscopy, intraocular pressure (IOP) measurements, and indirect ophthalmoscopy. The ex vivo microenvironmental vitreous pH was also monitored. Rabbits were euthanized at predetermined intervals and the residual devices, vitreous humor, and ocular tissue were retrieved and stored appropriately until further analysis. The DSMT was well tolerated up to 72 days and was still visible in the superotemporal quadrant of the eye. The mean IOP range (6-8 mmHg; N = 18) and changes in vitreous pH (7.25 ± 0.01; N = 3) correlated with baseline measurements. The DSMT displayed constant ganciclovir release at a rate of 2.02 μ g/h maintained within the 50% effective dose for human cytomegalovirus retinitis (N = 3). The design simplicity and application of the biodegradable DSMT device may provide a superior alternative for prolonged rate-controlled intraocular drug delivery.
authors.affiliation: University of the Witwatersrand, Department of Pharmacy and Pharmacology, Parktown 2193, Johannesburg, Gauteng, South Africa.
authors.forename: Yahya E
authors.initials: YE
authors.lastname: Choonara
authors.forename: Viness
authors.initials: V
authors.lastname: Pillay
authors.forename: Michael Paul
authors.initials: MP
authors.lastname: Danckwerts
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Carmichael
authors.forename: Leith C R
authors.initials: LC
authors.lastname: Meyer
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Du Toit
authors.forename: Simon
authors.initials: S
authors.lastname: Naylor
authors.forename: Carla
authors.initials: C
authors.lastname: Wanblad
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D003692:Delayed-Action Preparations / Q000737:chemistry; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D015774:Ganciclovir / Q000008:administration & dosage*; D006863:Hydrogen-Ion Concentration; D019344:Lactic Acid / Q000737:chemistry*; D008297:Male; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D057972:Posterior Eye Segment / Q000187:drug effects* / Q000648:ultrastructure; D011817:Rabbits
chemical_list: D000998:Antiviral Agents; D003692:Delayed-Action Preparations; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D015774:Ganciclovir